Heart failure management to avoid rehospitalization

ABSTRACT

Systems and methods are described for subject rehospitalization management. In an example, multiple physiologic signals can be obtained from a subject using multiple sensors. In response to a hospitalization event, pre-hospitalization characteristics of the multiple physiologic signals can be identified. Post-hospitalization characteristics of the multiple physiologic signals can be identified, including characteristics that differ from their corresponding pre-hospitalization characteristics. Later subsequent physiologic signals can be further monitored after the hospitalization event, such as using the same multiple sensors, and subsequent physiologic signal characteristics can be identified. In an example, a heart failure diagnostic indication can be determined using information about the pre-hospitalization characteristics, the post-hospitalization characteristics, and the subsequent characteristics. Information about relative changes in signal characteristics from multiple sensors can be used to identify particular subject physiologic signals to monitor during subsequent periods.

CLAIM OF PRIORITY

This application is a continuation of U.S. application Ser. No.16/223,798, filed Dec. 18, 2018, which is a continuation of U.S.application Ser. No. 15/058,613, filed Mar. 2, 2016, now issued as U.S.Pat. No. 10,182,767, which is a continuation of U.S. application Ser.No. 14/196,494, filed Mar. 4, 2014, now issued as U.S. Pat. No.9,339,231, which claims the benefit of priority under 35 U.S.C. § 119(e)of U.S. Provisional Patent Application Ser. No. 61/785,451, filed onMar. 14, 2013, and U.S. Provisional Patent Application Ser. No.61/856,816, filed on Jul. 22, 2013, each of which is herein incorporatedby reference in its entirety.

BACKGROUND

The heart is an electro-mechanical system performing two major pumpingfunctions. The left side of the heart, including the left atrium andleft ventricle, draws oxygenated blood from the lungs and pumps it tovarious organs of the body to provide the organs with oxygen for theirmetabolic needs. This pumped blood flow is called cardiac output. Theright side of the heart, including the right atrium and right ventricle,draws deoxygenated blood from the organs and pumps it into the lungswhere the blood gets oxygenated. The pumping functions are accomplishedby contractions of the myocardium (heart muscles). In a normal heart,the sinoatrial node, the heart's natural pacemaker, generates electricalimpulses, known as action potentials, which propagate through anelectrical conduction system to various regions of the heart to excitemyocardial tissues in these regions. Coordinated delays in thepropagations of the action potentials in a normal electrical conductionsystem cause various regions of the heart to contract in synchrony suchthat the pumping functions are performed efficiently.

A blocked or damaged electrical conduction system causes irregularcontractions of the myocardium, a condition generally known asarrhythmia. Arrhythmia reduces the heart's pumping efficiency and hence,diminishes the cardiac output. The diminished cardiac output can also becaused by heart failure, such as when the myocardium is weakened and itscontractility is reduced. A heart failure subject usually suffers fromboth a damaged electrical conduction system and deteriorated myocardium.

Heart failure has been recognized as a significant public health concernwith a huge economic impact. Subjects hospitalized with decompensatedheart failure reportedly have a high rate of rehospitalization withinsix months (more than 50% according to some studies), with a significantpercentage rehospitalized within a month. Hospital readmission is aprincipal factor responsible for the cost associated with managing heartfailure. Premature hospital discharge and insufficient resolution ofheart failure worsening are among the factors contributing to the highrate of rehospitalization. Therefore, there is a need to improvemanagement of heart failure hospitalization for reducing the rate ofrehospitalization. In an example, Wariar et al., in U.S. Pat. No.8,052,611, entitled METHOD AND APPARATUS FOR MANAGEMENT OF HEART FAILUREHOSPITALIZATION, refers generally to a hospitalization managementsystem.

OVERVIEW

Systems and methods are described for subject rehospitalizationmanagement. In an example, multiple physiologic signals can be obtainedfrom a subject using multiple sensors. In response to a hospitalizationevent, pre-hospitalization characteristics of the multiple physiologicsignals can be identified. Post-hospitalization characteristics of themultiple physiologic signals can be identified, includingcharacteristics that differ from their corresponding pre-hospitalizationcharacteristics. In an example, “corresponding” characteristics refersto like characteristics of a physiologic signal (e.g., peak amplitude,peak timing, etc.) obtained using the same sensor at different times.Later subsequent physiologic signals can be further monitored after thehospitalization event, such as using the same multiple sensors, andsubsequent physiologic signal characteristics can be identified. In anexample, a heart failure diagnostic indication can be determined usinginformation about the pre-hospitalization characteristics, thepost-hospitalization characteristics, and the subsequentcharacteristics.

The present inventors have recognized, among other things, that aproblem to be solved can include identifying subjects at risk forrehospitalization, such as before or after discharge from a hospital orother care facility. In an example, the present subject matter canprovide a solution to this problem by providing systems and methods toidentify a hospitalization event, identify pre-hospitalizationphysiologic characteristics from a subject physiologic signal, identifypost-hospitalization physiologic characteristics, from subjectphysiologic signals, that are different than the correspondingpre-hospitalization physiologic characteristics, and subsequentlymonitor the physiologic characteristics about the subject that aredifferent than the corresponding pre-hospitalization physiologiccharacteristics. In an example, the same subject physiologic sensor canbe used to identify the pre-hospitalization, post-hospitalization, andsubsequent monitored physiologic characteristics about the subject. Inan example, a heart failure parameter can be automatically determined toindicate worsening or improving heart failure status using informationabout the subsequently monitored characteristics relative to thepre-hospitalization or post-hospitalization characteristics.

In an example, the present subject matter can provide systems andmethods to receive pre-episode physiologic signal information about asubject from one or more physiologic sensors, and, after a treatment ortherapy event (e.g., a treatment or therapy event provided in responseto an episode), receive post-therapy physiologic signal informationabout the subject from the same one or more sensors. In an example, thepresent subject matter can provide systems and methods to receivesubsequent physiologic signal information using the same sensors used tocollect pre-episode and post-therapy information, and update a subjecttherapy, such as a therapy provided by an implantable medical device.The therapy can be updated using information about the subsequentphysiologic signal information relative to the pre-episode physiologicsignal information and the post-therapy physiologic signal information.

This overview is intended to provide an overview of subject matter ofthe present patent application. It is not intended to provide anexclusive or exhaustive explanation of the invention. The detaileddescription is included to provide further information about the presentpatent application.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, which are not necessarily drawn to scale, like numeralsmake describe similar components in different views. Like numeralshaving different letter suffixes may represent different instances ofsimilar components. The drawings illustrate generally, by way ofexample, but not by way of limitation, various embodiments discussed inthe present document.

FIG. 1 illustrates generally examples of implantable and externalmedical systems.

FIG. 2 illustrates generally an example of an implantable device coupledto multiple sensors.

FIG. 3 illustrates generally an example of multiple sensors in a subjectbody.

FIG. 4 illustrates generally examples of subject physiologic signalsover time.

FIG. 5 illustrates generally examples of subject physiologic signalsover time.

FIG. 6 illustrates generally an example that can include determining aheart failure parameter and providing a rehospitalization indication.

DETAILED DESCRIPTION

Heart failure subjects are generally most vulnerable for adverseoutcomes of adverse cardiac events in the first few days or weeksfollowing discharge from a hospital or following a treatment event.Given the recent trend of reducing provider reimbursement forrehospitalization of subjects within a specified period of timefollowing discharge (e.g., 30 days), it can be desirable to identifysubjects whose health status is declining following discharge, or atother times, and to optionally initiate, adjust, or otherwise optimizeone or more therapies available to the subject, such as by updating(e.g., changing) an operating characteristic of an implantable medicaldevice.

In an example, subjects with declining or unchanging health status canbe identified. For example, subjects who exhibit symptoms of worseningheart failure can be identified. In an example, one approach to identifysuch subjects includes tracking those aspects of a subject's clinicalstatus or physiology that change more than others during a subjecttherapy period, such as to determine if those aspects revert orotherwise change.

In an example, a subject is monitored by multiple sensors, such asbefore, during, or after a therapy event (e.g., a hospitalization event,clinical treatment, drug administration, etc.). Signals from somesensors may change more than others, such as between an identifiedadverse event (e.g., an episode on-set or hospitalization period) anddischarge. Such change can indicate a treatment effect on the subject.For example, a subject admitted for heart failure can be treated withdiuretics. If the treatment is effective, the subject may lose weightover the course of treatment. Accordingly, the subject's weight changeis an indication of the treatment effect on the subject.

In an example, characteristic information about a subject received fromsome sensors (e.g., sensors of a first type, such as weight sensors,oximetry sensors, heart rate sensors, ECG sensors, vessel pressuresensors, etc.) can change more than characteristic information about thesubject from other sensors (e.g., sensors of a different second type),such as in response to the same treatment or duration. In an example,the characteristic information that changes more, such as correspondingto a subset of available subject sensors, can represent an aspect of asubject clinic status or physiology that is most affected by, orresponsive to, the treatment (i.e., representative of the treatmenteffect). In an example, the subset of sensors that receive or providethe characteristic information that changes most can be furthermonitored, such as following subject discharge. If the characteristicinformation received by the subset of sensors changes by a predeterminedamount, such as toward the hospitalization values, an indication ofworsening subject health status can be provided, such as to indicatethat a subject treatment regimen is losing its efficacy or that thepatient is relapsing and may require rehospitalization. Such indicationscan be used to automatically change a subject therapy provided by animplantable medical device or other medical device.

In an example, as a subject approaches heart failure or other adversehealth events, subject characteristic information from multiple sensorsof different types are likely to change, such as to indicate worseningheart failure. As a subject undergoes treatment, such as in a hospitalor elsewhere, subject characteristic information from the sensors isgenerally expected to return to a baseline level at discharge. However,while some of the subject characteristic information corresponding tosome sensors may return to (or trend toward) baseline values, othersubject characteristic information corresponding to other sensors maynot, such as depending upon the appropriateness of the treatmentreceived by the subject, or the time course of sensor measurementresponding to treatment. In an example, subject characteristicinformation that returns to baseline can itself be used as dischargecriteria. In an example, if subject characteristic informationcorresponding to a subset of sensors does not return to baseline atdischarge (e.g., a sub-optimal discharge scenario), this information canrepresent a residual, or untreated portion of subject heart failure. Inan example, information from the subset of sensors can be expected togradually trend toward or return to baseline following discharge ortreatment. However, if the information from the subset of sensorspersists at the adverse hospitalization levels (e.g., within apredetermined amount of the difference between the baseline andhospitalization levels), then the information can indicate the subjectis not sufficiently recovering and may require rehospitalization.

In an example, a subject therapy can be provided or updated to attemptto avoid subject rehospitalization. For example, when arehospitalization alert is triggered by waning of treatment as describedabove, a device can be configured to iterate through programmingparameters to identify a set of parameters that is optimized to halt orinhibit any further subject reversion. For example, where a set ofsubject physiologic sensors is used to identify a treatment effectbecause information from the set of sensors changed the most betweenhospitalization and discharge, that set of sensors is representative ofthe subject response to treatment. If the information from the set ofsensors changes by a predetermined amount toward prior hospitalizationlevels, a device therapy can be automatically updated or optimized, suchas to select device parameters to reverse the adverse subject healthstatus trend. One example includes raising a lower rate limit in a CRTdevice, such as temporarily, to alleviate acute fluid overload.

In an example, when a rehospitalization alert is triggered by subjectphysiologic characteristic information lingering at hospitalizationlevels, a therapy can be similarly updated or optimized by adjusting adevice characteristic. In an example, updating a subject therapy caninclude adjusting one or more of an AV delay interval, a VV delayinterval, a lower rate pacing limit, an electrostimulation amplitudethreshold, an LV pacing electrode configuration (i.e. using quadrapolarleads), or changing a pacing mode, such as to or from a mode that israte-responsive or activity-responsive, or to or from a forced atrialpacing mode. Some examples of other device parameters that can beoptimized can include a pacing voltage, or a pacing pulse width, or apacing pulse shape, among others.

In an example, information from a heart sound sensor can be used, suchas to update or adjust one or more device parameters. In an example,information about heart sounds, such as heart sound intervals or othercharacteristics, can be used to adjust vagal or other neuralstimulation. Some characteristics of heart sounds that can indicate aneed for vagal stimulation can include a reduced S1 amplitude, anelevated S3 amplitude, a reduced R-S2 interval, an increased R-S1interval (pre-ejection period, or PEP), a decreased S1-S2 interval (HSejection time), or an increased PEP/HSET ratio.

Various implantable or external systems can include subject physiologicsensors that can be used to monitor one or more subject physiologicsignals. For example, FIG. 1 illustrates generally an example 100 of asubject 101 with an implantable system. The implantable system can beused to provide a subject therapy and detect or receive subjectphysiologic signal information, such as including impedance information,heart sound information, physiologic pulsatile signal information, orother information about the subject. In the example of FIG. 1, theimplantable system includes an implantable medical device (IMD) 105. Theimplantable medical device 105 can be configured to be coupled to one ormore of a first implantable lead system 108A and a second implantablelead system 108B. In an example, the first implantable lead system 108Ais configured to interact with nerve tissue or cervical vessels in thesubject body 101, and the second implantable lead system 108B isconfigured to interact with cardiac tissue. In an example, the IMD 105can be configured to use subject physiologic information, such asreceived from multiple subject sensors, to identify a subject healthstatus after an adverse health event and treatment. Combined cardiac andneuromodulation devices are further described in Amurthur et al., U.S.Pat. No. 7,664,548, entitled DISTRIBUTED NEUROMODULATION SYSTEM FORTREATMENT OF CARDIOVASCULAR DISEASE, Libbus et al., U.S. Pat. No.7,647,114, entitled BAROREFLEX MODULATION BASED ON MONITOREDCARDIOVASCULAR PARAMETER, and in Libbus et al., U.S. Pat. No. 8,005,543,entitled HEART FAILURE MANAGEMENT SYSTEM, which are incorporated hereinby reference in their entirety.

The IMD 105 can include a conductive housing 107 and a processor circuit110 operably connected to one or more stimulating or sensing circuits.The IMD 105 may be configured to operate autonomously with all circuitryresiding within the IMD 105, and/or may be configured to operate withone or more other devices (e.g., other IMD(s) and/or external device(s)such as a programmer or an analyzer circuit). The IMD 105 can beconfigured to deliver neural stimulation therapy and to communicate witha different cardiac rhythm management (CRM) device, such as a pacemakeror defibrillator, which can be configured to sense physiologicalparameter(s) or response(s) and provide cardiac rhythm managementtherapy.

In an example, the IMD 105 can include a communication circuit andantenna, or telemetry coil, such as can be used to communicatewirelessly with an external system 125 or other device. The system 100can include one or more leadless ECG electrodes 109 or other electrodes,such as can be disposed on the housing of the IMD 105. These electrodescan be used to detect heart rate or cardiac arrhythmias, among othercharacteristics of a cardiac cycle. For example, information receivedfrom the leadless ECG electrodes 109 can be analyzed by the processorcircuit 110 to identify features of a subject electrogram, such as toidentify fiducials or points of interest on a QRS complex. In anexample, a heart failure analysis module includes the IMD 105 and theexternal system 125. In an example, the heart failure analysis modulecan include one or more processor circuits, such as the processorcircuit 110 in the IMD 105 or one or more other processor circuits inthe external system 125 that can receive information from physiologicsensors and provide an indication of a subject health status, such as aheart failure parameter.

The external system 125 can include a remote medical device programmeror one or more other remote external modules (e.g., outside of wirelesscommunication range of the IMD 105 antenna, but coupled to the IMD 105using an external device, such as a repeater or network access point).The external system 125 can include a dedicated processor circuitconfigured to process information that can be sent to or received fromthe IMD 105. The information can include medical device programminginformation, subject data, device data, instructions, alerts, or otherinformation. In an example, the external system 125 includes an externaldevice 120 configured to display information (e.g., information receivedfrom the IMD 105) to a user. Further, the local programmer or the remoteprogrammer can be configured to communicate the sent or receivedinformation to a user or physician, such as by sending an alert (e.g.,via e-mail) of the status of the subject 101 or the system 100. In anexample, the processor circuit 110 in the IMD 105 or another processorcircuit in the external system 125 can be considered to be a portion ofa heart failure analysis module.

In an example, the IMD 105 can be coupled to a first implantable leadsystem 108A. The first implantable lead system 108A can include at leastone neural stimulation lead that can be subcutaneously implanted toposition electrode(s) to stimulate a neural target in a cervical region(e.g., in a region at or near the neck) in the subject body 101.Examples of cervical neural targets include a vagus nerve, a carotidsinus nerve, a hypoglossal nerve, a glossopharyngeal nerve, a phrenicnerve, baroreceptors and the nerves that innervate and are proximate tothe baroreceptors, and chemoreceptors and the nerves that innervate andare proximate to the chemoreceptors. The neural target may be on theleft side (e.g. left vagus nerve), or the right side (e.g. right vagusnerve). Additionally, bilateral neural targets may be stimulated. Otherneural stimulation lead(s) can include electrodes configured tostimulate neural targets outside of a cervical region. For example, anelectrode can be configured to stimulate a vagus nerve near the stomach.

Implanted electrode(s) disposed proximal to or in contact with a neuraltarget can be used to provide neural electrostimulation. A firstelectrode 111, such as a first nerve cuff electrode, can be disposed atthe end of the neural stimulation lead. In an example, the firstelectrode 111 can include a nerve cuff electrode that can be sized,shaped, or otherwise configured to be disposed around a vagus nerve 103.One or more additional nerve cuff electrodes, such as a second electrode112, can be similarly provided. In an example, neural stimulation may beprovided using the first and second electrodes 111 and 112 in a bipolarconfiguration. In an example, neural or muscular electrical activity canbe detected using the first and second electrodes 111 and 112, or anelectrical response signal can be provided and/or detected using thefirst and second electrodes 111 and 112.

Some other vagus nerve stimulation examples can include one or moreelectrodes that can be sized, shaped, or otherwise configured to be fedinto a vessel near the vagus nerve 103, such as for using electrodespositioned within the vessel to intravascularly stimulate the neuraltarget. For example, a neural target can be stimulated using at leastone electrode positioned internally within a jugular vein 102 or acarotid artery 104. The neural stimulation may be bipolar stimulation orunipolar stimulation, such as where the conductive housing 107 of theIMD 105 functions as an electrode.

In an example, such as shown in FIG. 1, the IMD 105 can be coupled to asecond implantable lead system 108B. The second implantable lead system108B can include a cardiac electrostimulation stimulation lead that canbe subcutaneously implanted to position one or more electrodes tostimulate cardiac tissue, such as myocardial or neural cardiac tissue.In an example, the second implantable lead system 108B can includemultiple atrial and ventricular leads that each includes one or moreelectrodes for pacing and/or cardioversion/defibrillation.

The example of FIG. 1 further includes an external system 125, and atelemetry link 115 that provides bidirectional communication between theIMD 105 and the external system 125. In an example, the external system125 includes a programmer. In another example, as illustrated in FIG. 1,the external system 125 can be a patient management system including anexternal device 120 in proximity of the IMD 105, a remote device 124 ina location relatively distant from the IMD 105, and a telecommunicationnetwork 122 linking the external device 120 and the remote device 124.In an example, the external system 125 is a patient management systemthat allows access to the IMD 105 from a remote location, such as formonitoring subject status or adjusting a subject therapy or deviceparameter.

In an example, the telemetry link 115 is an inductive telemetry link. Inanother embodiment, the telemetry link 115 is a far-fieldradio-frequency (RF) telemetry link. The telemetry link 115 provides fordata transmission from the IMD 105 to the external system 125. This mayinclude, for example, transmitting real-time physiological data acquiredby the IMD 105, extracting physiological data acquired by and stored inthe IMD 105, extracting subject history data such as data indicative ofoccurrences of arrhythmias, occurrences of decompensation, and therapydeliveries recorded in the IMD 105, and extracting data indicating anoperational status of the IMD 105 (e.g., battery status and leadimpedance). The telemetry link 115 also provides for data transmissionfrom the external system 125 to the IMD 105. This may include, forexample, programming the IMD 105 to acquire physiological data using oneor more subject sensors, programming the IMD 105 to perform at least oneself-diagnostic test (such as for identifying or determining a deviceoperational status), programming the IMD 105 to deliver at least onetherapy, or instructing the IMD 105 to analyze data associated withheart failure.

In an example, at least one of the IMD 105 and the external system 125includes a heart failure analyzer that can provide hospitalizationmanagement for a heart failure subject using at least diagnostic dataacquired by the IMD 105. The heart failure analyzer can analyze subjectdiagnostic data for therapy monitoring, risk stratification, anddischarge planning during hospitalization of a heart failure subject,and for monitoring and intervention after the hospitalization of thesubject (e.g., in a post-hospitalization or post-episode mode). In someexamples, at least a portion of the heart failure analyzer is providedin both the IMD 105 and the external system 125. The heart failureanalyzer can be implemented using a combination of hardware andsoftware. In some examples, each element of the heart failure analyzer,including its specific embodiments, is implemented using anapplication-specific circuit constructed to perform one or moreparticular functions or a general-purpose circuit programmed to performsuch function(s). Such a general-purpose circuit includes, but is notlimited to, a microprocessor or a portion thereof, a microcontroller orportions thereof, and a programmable logic circuit or a portion thereof,such as can be configured to receive or archive information about thesubject received from one or more sensors.

FIG. 2 illustrates generally an example of the IMD 105. The IMD 105includes the processor circuit 110. The IMD 105 further includes anelectrical energy delivery circuit 250, such as can be configured to usea constant current or voltage source to deliver an electrical signalbetween two or more electrodes (e.g., using one or more electrodesincluded in the first or second implantable lead systems 108A and 108B),such as disposed in a cervical, thoracic, cardiac, or other body region.In an example, the electrical delivery circuit 250 is coupled to aneural electrostimulation circuit comprising implanted and/or externalelectrodes 251 configured to provide electrostimulation to neuraltargets. In an example, the electrical delivery circuit 250 is coupledto a cardiac electrostimulation circuit comprising the implanted and/orexternal electrodes 251 configured to provide electrostimulation in ornear a subject heart. In the example of FIG. 2, a telemetry circuit 235is connected to the processor circuit 110. The telemetry circuit 235 cantransmit data from the IMD 105 to an adjunct system, such as theexternal device 120. Transmitted data can include, among other things,data from one or more sensors coupled to the IMD 105, diagnosticinformation generated by the IV 105, or device configuration orprogramming information about the IMD 105.

In an example, the processor circuit 110 is coupled to one or morephysiologic sensors, such as using multiple sensor data inputs. Forexample, a data input of the processor circuit 110 can be coupled to oneor more of an acoustic sensor 201, a device-based or other ECG sensor202, a vibration sensor 203, a hemodynamic sensor 204, an impedancesensor 205, a respiration sensor 206, a chemical sensor 207, a posturesensor 208, or other physiologic sensor 209. In an example, theprocessor circuit 110 is configured to calculate or derive subjectphysiologic information (e.g., ejection fraction, pre-ejection period,etc.) using information received from one or more of the physiologicsensors. In an example, the processor circuit 110 includes a data outputconfigured to provide a heart failure parameter about the subject,including a quantification of a subject's worsening or improving healthstatus.

In an example, an acoustic sensor 201 is coupled to the processorcircuit 110. The acoustic sensor 201 can be an implantable or externaltransducer, such as a microphone or accelerometer. The acoustic sensor201 can be configured to receive acoustic vibrational energy from asubject, such as in the audible spectrum. In an example, a portion ofthe processor circuit 110 can be configured to receive information fromthe acoustic sensor 201 and identify one or more of heart soundinformation, respiration information, or other physiologic information.For example, information from the acoustic sensor 201 can be used toidentify an S1 heart sound timing or amplitude characteristic, or toidentify a presence of an S3 or S4 heart sound.

In an example, an ECG sensor 202 is coupled to the processor circuit110. The ECG sensor 202 can be an implantable or external sensor. Forexample, the ECG sensor 202 can include at least two electrodes disposedin or on the subject body 101 and configured to detect electricalactivity from the subject body 101. In an example, the ECG sensor 202includes two implanted electrodes (e.g., a can electrode and a remoteelectrode disposed in or on the heart 106, such as included in thesecond implantable lead system 108B) in the subject body 101. Theprocessor circuit 110 can be configured to receive electrograminformation from the ECG sensor 202. In an example, the processorcircuit 110 can use the received electrogram information to identifymorphological characteristics (e.g., timings, amplitudes, shapes, etc.)of a subject QRS complex.

In an example, a vibration sensor 203 is coupled to the processorcircuit 110. The vibration sensor 203 can be an implantable or externaltransducer, such as an accelerometer. The vibration sensor 203 can beconfigured to receive vibrational energy from a subject, such as can beused to identify one or more of cardiac activity, respiratory activity,or other subject physical activity level, such as a relative exercise orexertion level. In an example, a portion of the processor circuit 110can be configured to receive information from the vibration sensor 203and identify one or more of heart sound information, respirationinformation, or other physiologic information.

In an example, a hemodynamic sensor 204 is coupled to the processorcircuit 110. The hemodynamic sensor 204 can be an implantable orexternal pressure sensor, such as an implantable sensor configured tocontinuously or intermittently monitor intracardiac or vessel pressures.In an example, the hemodynamic sensor 204 can include a pressure sensorcoupled to an RV or atrial lead of the IMD 105, or the hemodynamicsensor 204 can alternatively or additionally include a pressure sensordisposed in a pulmonary artery. The processor circuit 110 can beconfigured to receive pressure information from the hemodynamic sensor204.

In an example, an impedance sensor 205 is coupled to the processorcircuit 110. The impedance sensor 205 can be implantable or external tothe subject body 101, or can include both implantable and externalportions. In an example, the impedance sensor 205 includes at least twoelectrodes disposed in or on the subject body 101 and configured todetect responsive electrical signals from the subject body 101, such asin response to a non-tissue-stimulating electrostimulation provided tothe subject body 101 using the same or different at least twoelectrodes. In an example, the impedance sensor 205 includes twoimplanted electrodes (e.g., a can electrode and a remote electrodedisposed in or on the heart 106, such as included in the secondimplantable lead system 108B) in the subject body 101. The processorcircuit 110 can be configured to receive electrical signal informationfrom the impedance sensor 205 to identify a detected or measuredimpedance between the two or more electrodes. In an example, theprocessor circuit 110 can use the received impedance information toidentify cardiac activity, respiratory activity, muscle activity,thoracic fluid level, vessel dimensional changes (e.g., using impedanceplethysmography techniques), or other information about a subjectphysiologic status.

In an example, a respiration sensor 206 is coupled to the processorcircuit 110. The respiration sensor 206 can be an implantable orexternal respiration sensor, such as an implantable sensor configured tomonitor subject chest expansion and contraction. In an example, therespiration sensor 206 can be configured to provide information about asubject tidal volume or minute ventilation. The processor circuit 110can be configured to receive respiratory information from therespiration sensor 206.

In an example, a chemical sensor 207 is coupled to the processor circuit110. The chemical sensor 207 can be an implantable or external sensorconfigured to identify one or more biomarkers. For example, the chemicalsensor 207 can be configured to detect subject chemistry information,such as including information about one or more of a subject bloodchemistry (e.g., electrolytes, glucose, pH, oxygen level, carbon dioxidelevel, etc.), natriuretic peptides (i.e., B-type natriuretic peptide(BNP), N-terminal proBNP, atrial natriuretic peptide, etc.),inflammatory markers, oxidative stress markers, or collagen turnover orextracellular matrix peptides, among other information. The processorcircuit 110 can be configured to receive subject chemistry informationfrom the chemical sensor 207.

In an example, a posture sensor 208 is coupled to the processor circuit110. The posture sensor 208 can be an implantable or external posturesensor configured to detect, determine, or differentiate between patientpostures. For example, the posture sensor 208 can include anaccelerometer configured to provide information about whether the sensor(e.g., installed in or otherwise coupled to the subject) is verticallyor horizontally oriented. In an example, the posture sensor 208 includesan impedance sensor, such as configured to measure a thoracic or vesselimpedance from which subject orientation can be determined. Theprocessor circuit 110 can be configured to receive subject postureinformation from the posture sensor 208.

In an example, other physiologic sensors 209 can be coupled to theprocessor circuit 110 to receive information about a physiologic orhealth status of a subject.

A memory circuit 235 can be coupled to the processor circuit 110 and/orto one or more of the physiologic sensors 201-209, such as to recordsubject physiologic information overtime. In an example, the processorcircuit 110 can access subject physiologic information stored in thememory circuit 240, such as to identify changes or trends in the subjectphysiologic information over time. For example, heart sound amplitudeinformation received using the acoustic sensor 201 can be stored in thememory circuit 240 and trended over time using the processor circuit110, such as to identify increasing or decreasing heart sound amplitudeover time. The processor circuit 110 can modify or otherwise processinformation stored in the memory circuit 240, such as to transform oneor more physiologic signals. For example, the processor circuit 110 canbe configured to generate, for example, one or more of a derivativewaveform, a filtered waveform, or an integrated waveform of an impedancesignal sensed by the impedance sensor 205. Such transformation can beimplemented with, for example, a differentiator, a filter (e.g., linear,high pass, low pass, band pass), a derivative circuit, or an integratorcircuit, among others, such as can be integrated with or coupled to theprocessor circuit 110.

In an example, the systems described above in the discussion of FIGS. 1and 2, such as including the external system 125 and the IMD 105, amongother systems, can be used to monitor or receive physiologic signalsfrom a subject using one or more subject physiologic sensors. Theexternal system 125 or the IMD 105 can be configured to identify orreceive an indication of a hospitalization event or indication of someother adverse subject health episode (herein generally referred to as a“hospitalization event”). In response to the hospitalization event, orbefore the hospitalization event, the processor circuit 110 (or asimilar processor in a portion of the external system 125) can beconfigured to identify, in one or more received physiologic signals,pre-hospitalization physiologic signal characteristics. In someexamples, pre-hospitalization can also include “at arrival” to ahospitalization event. In some situations, the information for thepre-hospitalization period may be limited to the data available when thesubject is identified with worsening heart failure or other condition,such as when a subject first contacts a caregiver, or first arrives at ahospital or other treatment facility. In this example, the initialmeasurement at the time of hospitalization can be considered and used asinformation corresponding to the pre-hospitalization period.

In an example, the processor circuit 110 can be configured to receive animpedance signal from the impedance sensor 205 before thehospitalization event, and the processor circuit 110 can be configuredto identify one or more characteristics of the impedance signal (e.g., apeak amplitude, a peak timing, a peak change timing, an amplitude at aparticular time point within a cardiac cycle, an average impedance overa predetermined duration, a thoracic fluid level estimate, etc.) duringthe pre-hospitalization period. In this example, the processor circuit110 can be configured to receive the same or different impedance signal(e.g., using the same electrodes) during a “post-hospitalization”period. In an example, the post-hospitalization period includes aduration following the hospitalization event when a subject is at ahospital or undergoing a treatment. Following treatment during thepost-hospitalization period, a subsequent period can include a periodafter the subject is discharged from the hospital or after the subjecthas undergone a particular therapy or device modification. For example,during the post-hospitalization period, one or more operatingcharacteristics of a subject's IMD can be adjusted (e.g., an AV delay ina CRT device is decreased, or a lower rate limit is increased), andduring the subsequent period, one or more physiologic signals from thesubject can be monitored to identify subject characteristics that change(or do not change) in response to the IMD adjustment.

In an example, information about the changed and unchanged subjectcharacteristics can be used to determine a heart failure parameter forthe subject, such as using the processor circuit 110 (or anotherprocessor circuit, such as included in the external system 125). In anexample, the heart failure parameter is provided using information abouta subsequent physiologic signal characteristic relative to itscorresponding pre-hospitalization physiologic signal characteristic. Inan example, the heart failure parameter is an indication of an overallsubject health status, such as can be used to provide a dischargerecommendation.

In an example, the heart failure parameter can be used to identifyworsening heart failure and, depending on the sensors used to determinethe heart failure parameter, various subject therapies can beimplemented or changed, such as automatically by the processor circuit110. In an example, in response to the heart failure parameterindicating worsening heart failure, a lower rate limit of the IMD 105can be raised, such as temporarily to alleviate symptoms. In an example,in response to worsening heart failure, a pacing amplitude or pacingwaveform shape can be changed. For example, an amplitude can beincreased, or a duration of one or both portions of a biphasic waveformcan be increased or decreased. In an example, in response to worseningheart failure, an electrostimulation application location can bechanged. For example, using a multipolar lead, different combinations ofelectrodes (e.g., corresponding to a left ventricle) can be selected.

Referring now to FIG. 3, the subject body 101 is shown with severalphysiologic sensors coupled to the IMD 105. In an example, the IMD 105is coupled to a first sensor 301 (denoted S₁), a second sensor 302(denoted S₂), a third sensor 303 (denoted S₃), and a fourth sensor 304(denoted S₄). In other examples, the IMD 105 is coupled to as few as onesensor, and in still other examples, the IMD 105 is coupled to two ormore sensors.

In the example of FIG. 3, the first sensor 301 is a heart sound sensor(e.g., implemented using the acoustic sensor 201 or the vibration sensor203), the second sensor 302 is a thoracic impedance sensor (e.g.,implemented using the impedance sensor 205), and the third sensor 303 isa pulmonary artery pressure sensor (e.g., implemented using thehemodynamic sensor 204 disposed in a subject pulmonary artery, orimplemented using the impedance sensor 205 configured to measuredimensional changes of the subject pulmonary artery, among other). In anexample, the fourth sensor 404 is a left ventricle ejection fractionsensor implemented using the processor circuit 110, such as to computethe ejection fraction using information obtained in part from the ECGsensor 202.

FIG. 4 illustrates generally examples of charts showing physiologicinformation received from the sensors illustrated in FIG. 3. Theexamples in FIG. 4 include first, second, third, and fourth charts 401,402, 403, and 404, corresponding to physiologic signal informationreceived respectively from the first, second, third, and fourth sensors301, 302, 303, and 304. In the example of FIG. 4, the sensor informationrepresented in each of the first, second, third, and fourth charts 401,402, 403, and 404 corresponds to the same time interval along the xaxis. The time interval includes a pre-hospitalization period 411 (e.g.,a duration before a subject hospitalization or health event), followedby a post-hospitalization period 412 (e.g., a duration during which asubject is undergoing treatment, such as at a hospital), followed by asubsequent period 413 (e.g., a duration after the treatment during thepost-hospitalization period 412, such as after discharge from thehospital).

The first chart 401 illustrates generally a first physiologic signal 421corresponding to a subject heart sound amplitude (e.g., an S1 heartsound amplitude) over time as a percentage of a predetermined baselineheart sound amplitude (e.g., a subject-specific or population-specificbaseline, such as normalized to 100%). In the example of the first chart401, they axis can be divided into several regions corresponding tosubject health status inferred from the first physiologic signal 421information. The first chart includes a first region, S_(1H),corresponding to S1 heart sound amplitudes that represent a healthysubject, a second region, S_(1N), corresponding to S1 heart soundamplitudes that represent borderline, worsening, or neutral subjecthealth status, and a third region, S_(1Z), corresponding to S1 heartsound amplitudes that represent poor subject health status. In anexample, when the data from the first physiologic signal 421 correspondsto the third region, S_(1Z), a need for treatment or hospitalization canbe indicated. In the example of FIG. 4, the first region, S_(1H),corresponds to heart sound amplitudes that are 95% or more of baseline,the second region, S_(1N), corresponds to heart sound amplitudes between75% and 95% of baseline, and the third region, S_(1Z), corresponds toheart sound amplitudes below 75% of baseline. The various regions can besubject-specific, such as determined automatically using an algorithmexecuted by the processor circuit 110, or determined manually by acaregiver. In some examples, the regions are population-specific, or theregions are pre-defined.

In the example of the first chart 401, the first physiologic signal 421rapidly declines over the pre-hospitalization period 411 from thebaseline heart sound amplitude (e.g., where baseline is normalized to100/6) to a minimum heart sound amplitude of about 69%, corresponding tothe third region, S_(1Z). In an example, when the first physiologicsignal 421 indicates a heart sound amplitude in the third region,S_(1Z), an alert can be provided, such as automatically to the subjector a caregiver, such as using the IMD 105 (e.g., using an audiblealert), or using the external system 125 (e.g., using an externalinterface, such as including a remote patient care management system).

The second, third, and fourth charts 402, 403, and 404, includerespective second, third, and fourth physiologic signals 422, 423, and424. Similarly to the description above regarding the first chart 401,each of the second, third, and fourth charts 402, 403, and 404, includerespective regions along they axis that represent different subjecthealth statuses (see, e.g., the second chart 402 at regions S_(2H),S_(2N), S_(2Z), etc.). In the example of FIG. 4, each of the first,second, third, and fourth physiologic signals 421, 422, 423, and 424,indicate hospitalization or treatment for the subject at the end of thepre-hospitalization period 411.

In the example of FIG. 4, at the onset of the post-hospitalizationperiod 412, subject health status is indicated to be poor by each of thefirst, second, third, and fourth physiologic signals 421, 422, 423, and424. In an example, the post-hospitalization period 412 includes atreatment event (such as at or near the beginning of the period). Overthe course of the post-hospitalization period 412, information from oneor more of the sensors can indicate improving subject health status,such as where a corresponding subject physiologic signal trends towardor returns to its baseline.

In the example of FIG. 4, during the post-hospitalization period 412,the first and third physiologic signals 421 and 423 remain in the S_(1Z)and S_(3Z) regions, respectively, corresponding to an indication forfurther treatment or continued hospitalization. The second and fourthphysiologic signals 422 and 424 return to their respective baselineS_(2H) and S_(4H) regions over the same interval, corresponding toimproving subject health status. In an example, it can be determined(e.g., automatically by a medical device or manually by a caregiver)that the subject health status is sufficiently improved or stabilized(as indicated by the return of the second and fourth physiologic signals422 and 424 to baseline), and the subject can be discharged, or thetreatment can be terminated. For example, where the treatment eventincludes administering a pharmacologic diuretic, the diuretic can bediscontinued. Subject discharge from the hospital or termination of atherapy can indicate an end of the post-hospitalization period 412. Insome examples, other treatments can be provided, such as to address anyresidual subject health status issues, such as represented by the firstand third physiologic signals 421 and 423 which remain at less thanoptimal levels at the end of the post-hospitalization period 412.

In the example of FIG. 4, at the end of the post-hospitalization period412, sensors can be identified that correspond to physiologic signalsthat indicate aspects of a subject physiology that were not responsiveto treatment, or that responded negatively to treatment (e.g., byindicating worsening subject health status). Similarly, sensorscorresponding to physiologic signals that indicate aspects of a subjectphysiology that were responsive to treatment can be identified. Thesesensors can be identified automatically, such as using the processorcircuit 110 to analyze the subject physiologic signal information. Thesensors corresponding to physiologic signals that were responsive totreatment can be used for subsequent subject health status assessment,such as in the subsequent period 413.

In the example of FIG. 4, during the subsequent period 413, the secondand fourth physiologic signals 422 and 424 can be monitored, such asusing the processor circuit 110. In the example of the second and fourthcharts 402 and 404, the second and fourth physiologic signals 422 and424 decline from the S_(2H) and S_(4H) baseline regions, respectively.In this example, the second and fourth physiologic signals 422 and 424decline to the S_(2N) and S_(4N) regions, respectively. These trendsaway from the signals' respective baseline regions indicate subjecthealth status is declining. In an example, an alert can be provided to asubject or caregiver when one or both of the second and fourthphysiologic signals 422 and 424 change by more than a predeterminedthreshold amount, such as to indicate a possible imminentrehospitalization or a need for a different or adjusted therapy.

In an example, where a particular treatment regimen is initiated duringthe post-hospitalization period 412 and carried on through thesubsequent period 413, the declining health status represented by thesecond and fourth physiologic signals 422 and 424 over the subsequentperiod 413 can represent that the particular therapy regimen is losingits effectiveness. In an example, the particular therapy regimen caninclude a device therapy (e.g., a pacing therapy) that can beautomatically or manually updated in response to the change in one ormore physiologic signals. In an example, rehospitalization can beindicated in response to the declining subject health status indicatedby the second and fourth physiologic signals 422 and 424, such as beforethe signals reach their respective S_(2Z) and S_(4Z) regions.

In an example, during the subsequent period 413, therapies configured toaddress the conditions monitored by S2 and S4 can be initiated inresponse to the declining subject health status indicated by the secondand fourth physiologic signals 422 and 424. For example, in FIG. 4, thesecond physiologic signal 422 represents a subject thoracic impedancerelative to a baseline impedance, and is indicative of a subjectthoracic fluid level. In response to the decline of the secondphysiologic signal 422 from about 91% of baseline at the beginning ofthe subsequent period 413 to about 71% of baseline later in thesubsequent period 413 (e.g., indicative of an increase in thoracic fluidlevel), an operating characteristic of the IMD 105 can be adjusted(e.g., a lower rate limit can be increased) to attempt to reduce thethoracic fluid level. In an example, such a therapy adjustment can beperformed automatically by the IMD 105, or can be performed manually bya clinician or other caregiver. In an example, a therapy adjustment canbe performed remotely using the external system 125, such as in responseto an alert generated by the external system 125 in response to thesubject physiologic signals.

FIG. 5 illustrates generally an example of a fifth chart 405corresponding to physiologic signal information received from the firstsensor 301. The fifth chart 405 includes fifth and sixth physiologicsignals 425 and 426. In the example of FIG. 5, the fifth and sixthphysiologic signals 425 and 426 are alternative signals corresponding todifferent theoretical subject health statuses for a subject over acommon time period (e.g., over the post-hospitalization period). In thisexample, the time period is further divided into equal durationintervals denoted t₁, t₂, and t₃.

In an example, the fifth chart 405 illustrates a post-hospitalizationperiod that includes a subject treatment event (e.g., a pharmacological,device-based, or other therapy or treatment). In an example, the subjectphysiologic signal over the post-hospitalization period is representedby the fifth physiologic signal 425. In this example, the subject heartsound amplitude improves over the post-hospitalization period, fromabout 64% of baseline at the beginning of the period to about 75% ofbaseline at the end of the period. Thus, in this example, the subjectheart sound amplitude indicates an improving subject health status asthe heart sound amplitude characteristic trends toward the desired 100%of baseline.

In an example, the fifth chart 405 illustrates a subsequent period(e.g., a period following the post-hospitalization period, such as afterdischarge or after treatment), and the fifth physiologic signal 425indicates improving subject health status under the therapy or regimenreceived by the subject over the subsequent period. For example, where alower rate limit of the IMD 105 was increased in a prior period (e.g.,in a post-hospitalization period), the trend of the fifth physiologicsignal 425 over the subsequent period can indicate that the lower ratelimit adjustment is effective and should be maintained.

In an example, the subject physiologic signal over thepost-hospitalization period is represented by the sixth physiologicsignal 426. In this example, the subject heart sound amplitude isrelatively unchanged over the post-hospitalization period. That is, thesixth physiologic signal 426 begins the post-hospitalization period andends the post-hospitalization period at about 65% or less of baseline.Because the subject physiologic status is generally expected to improveover the period, the unchanged characteristic of the signal canrepresent a residual or untreated portion of the subject physiology, andrehospitalization or therapy adjustment can be indicated. Some subjectcharacteristics indicative of an untreated portion of subject heartfailure can include unchanged heart sound signal characteristics,unchanged respiration rate, and unchanged tidal volume, among others.

In an example, a subject physiologic signal can be monitored for changesin magnitude by at least a predetermined threshold amount, such as overa specified period. Generally, the information received from aparticular physiologic sensor is expected to trend toward its baselinevalue as subject status improves. However, if information from aparticular sensor is static (e.g., the subject physiologiccharacteristic monitored by the particular sensor remains within ahospitalization range, such as over a specified duration), the subjectcan be deemed to be not adequately recovering and a risk for subjectrehospitalization can be assessed.

In the example of FIG. 5, a rehospitalization alert can be provided whenthe subject physiologic signal does not improve by the threshold amountover the specified period. In an example, if the subject physiologicsignal does not exceed 70% within the first interval t₁, then arehospitalization or other alert can be provided. In this example,because neither the fifth or sixth physiologic signals 425 or 426exceeds 70% within the first interval t₁, a rehospitalization or otheralert can be provided. In an example, if the subject physiologic signaldoes not exceed 70% before the end of the second interval t₂, therehospitalization or other alert can be provided. In this example, thefifth physiologic signal 425 exceeds the threshold amount of 70% cbefore the end of the second interval t₂. Accordingly, the alert can beavoided, or withheld for further monitoring. The sixth physiologicsignal 426 does not exceed the threshold 70% before the end of thesecond interval t₂, and, accordingly, the alert can be provided.

Referring now to FIG. 6, an example 600 includes determining a heartfailure parameter and providing a rehospitalization indication. At 610,the example 600 includes monitoring multiple physiologic signals from asubject, over a pre-hospitalization period, using respective multiplesensors. For example, at 610, the monitored physiologic signals caninclude, among others, heart sound signals, electrophysiologic signals,or hemodynamic signals, such as received from the subject using anacoustic sensor, implanted electrodes, or a pressure transducer,respectively. In an example, the IMD 105 or the external system 125includes a memory circuit configured to store information about themonitored multiple physiologic signals, such as by periodically samplinga continuous physiologic signal or by using histogram-based storagetechniques to store information about a sampled physiologic signal.

At 615, a hospitalization event can be identified. Throughout thisdocument, a hospitalization event refers to any adverse subject healthevent, such as a heart failure decompensation episode, or other event,episode, symptom, or trend that indicates a subject's health status isdeclining. For example, a hospitalization event can refer to a time whena heart failure subject seeks treatment for accumulated thoracic fluid.In some examples, a hospitalization event refers to subject admission toa hospital or other treatment facility. In some examples, ahospitalization event refers to an acute or even temporary symptom, suchas chest pain or difficulty breathing.

At 620, pre-hospitalization physiologic signal characteristics can beidentified. In an example, the IMD 105 or the external system 125includes a memory circuit configured to store information about recentsubject physiologic signal activity from multiple subject sensors. Forexample, the IMD 105 can include a memory circuit configured to recordthe last seven days (or more) of subject physiologic signal activityfrom each of a heart sound sensor and an ECG sensor (e.g., at the sameor different sample rates). In response to the hospitalization eventidentified at 615, the processor circuit 110 can analyze the recordedsubject physiologic signals to identify various characteristics of thesignals. For example, the processor circuit 110 (or other processingmodule, such as included in the external system 125) can analyze therecorded heart sound signal and identify an S1 amplitude characteristicover the recorded period. The processor circuit 110 can trend thecharacteristic information to determine whether the characteristic canbe correlated to the hospitalization event or the subject health status.Similarly, the processor circuit 110 can analyze the recorded ECG signaland identify a QRS width characteristic over the recorded period. TheQRS width can be analyzed (e.g., automatically by the processor circuit,or by a caregiver) to determine whether the QRS width characteristic canbe correlated to the hospitalization event or the subject health status.

At 630, post-hospitalization physiologic signal characteristics can beidentified over a post-hospitalization period. The post-hospitalizationperiod corresponds to a period following the hospitalization event. Insome examples, the post-hospitalization period includes a period when asubject is at a hospital or other care facility, and in some examplesthe post-hospitalization period includes a period when a subject isundergoing a treatment regimen (e.g., implemented automatically by theIMD 105 in response to the identified hospitalization event at 615).

At 630, the processor circuit 110 can continue to monitor the subjectphysiologic signals using the same sensors that were used to receive thepre-hospitalization physiologic signals. Characteristics of thepost-hospitalization physiologic signals can be identified, such ascharacteristics of the same or different type than the characteristicsof the pre-hospitalization physiologic signals. For example, thepost-hospitalization physiologic signals can include a heart soundsignal that can be analyzed to identify S1 amplitude characteristicsover the post-hospitalization period. Similarly, thepost-hospitalization physiologic signals can include an ECG signal thatcan be analyzed to identify QRS width information over thepost-hospitalization period.

At 640, one or more subsequent physiologic signals can be monitored overa subsequent period, such as using the same multiple sensors used tomonitor the multiple physiologic signals at 610. The subsequentphysiologic signals can be signals monitored after thepost-hospitalization period. In some examples, the subsequent periodincludes a period after subject discharge from a hospital or other carefacility, or the subsequent period includes a period after a subjecttherapy is updated. For example, the subsequent period can include aperiod after a lower rate limit of a subject pacemaker device is raised.

In an example, physiologic signal information from a portion of theavailable subject sensors is used in the monitoring at 640. For example,where a monitored characteristic of a physiologic signal, received froma particular sensor, changes over the post-hospitalization period (e.g.,relative to the pre-hospitalization period), subsequent physiologicsignal information from that same sensor can be flagged for furthermonitoring. In an example, signal characteristics that change over thepost-hospitalization period can indicate a treatment effect.

At 650, a subsequent physiologic signal characteristic can be identifiedusing the one or more subsequent physiologic signals received over thesubsequent period. In an example where the subject heart sound amplitudechanges over the post-hospitalization period, the subject heart soundsignal can be indicated for further monitoring and analysis over thesubsequent period. In an example where the subject QRS duration isshorter over the post-hospitalization period relative to thepre-hospitalization period, the subject ECG signal can be indicated forfurther monitoring and analysis over the subsequent period. Subsequentcharacteristics of the heart sound signal and ECG signal, such asmonitored over the subsequent period, can be identified at 650.

At 660, information about the subsequent physiologic signalcharacteristic identified at 650 can be compared to a correspondingpre-hospitalization physiologic signal characteristic or to acorresponding post-hospitalization physiologic signal characteristic.For example, where S1 heart sound amplitude is used, characteristicinformation about the S1 heart sound amplitude over the subsequentperiod (e.g., average peak amplitude) can be compared to one or both ofthe S1 heart sound amplitude from the pre-hospitalization period and theS1 heart sound amplitude from the post-hospitalization period.

In an example, at 670, a heart failure parameter can be determined. Theheart failure parameter can be an absolute or relative indication of asubject health status that can be determined using a comparison ofphysiologic signal characteristics over time. For example, where thecharacteristic compared at 660 is S1 heart sound amplitude, the heartfailure parameter can indicate worsening subject heart failure when thepost-hospitalization S1 amplitude characteristic indicates poor subjecthealth status (e.g., S1 amplitude is at 60% of baseline) and thesubsequent S1 amplitude characteristic indicates no change from thepost-hospitalization period (e.g., S1 amplitude remains at or about 60%of baseline), such as after the subject undergoes treatment or after thesubject receives a therapy adjustment.

At 672, a subject discharge recommendation can be provided, such asusing the heart failure parameter determined at 670. For example, wherethe subsequent period includes a period when the subject remains in acare facility, such as after undergoing a medical procedure or receivinga device therapy update, the information about the heart failureparameter determined at 670 can be used to determine or influence adischarge decision. In an example, a discharge alert can be providedautomatically using the IMD 105 or the external system 125, or thedischarge recommendation can be determined manually by a caregiver, suchas in response to the information about the determined heart failureparameter.

At 674, a subject therapy parameter can be updated, such as using theheart failure parameter determined at 670. The therapy parameter updatecan be performed automatically using the processor circuit 110, ormanually by a caregiver who interacts with the external system 125. Inan example where the heart failure parameter determined at 670 indicatesworsening heart failure, therapy parameters that can be updated at 674can include a lower or upper pacing rate limit, a diuretic drugadministration regimen, a VV delay, an AV delay, an initiation ortermination of a neural modulation therapy, or an adjustment to anelectrostimulation amplitude, among others.

In an example, at 680, a trend of a subject physiologic signal or signalcharacteristic can be identified. For example, the subsequentphysiologic signal, or a characteristic thereof, can be trended todetermine whether the signal or characteristic trends toward a subjectpre-hospitalization characteristic, such as described above in thediscussion of FIG. 5. In an example, the subsequent physiologic signalor characteristic is trended to identify whether the characteristic isapproaching the same level or quantity as was measured when thehospitalization event was identified at 615. In an example where thesubsequent physiologic signal or characteristic trends toward thesubject pre-hospitalization characteristic, a subject rehospitalizationindication can be provided at 682. The subject rehospitalizationindication can be provided using the IMD 105 (e.g., using an audiblealert) or using the external system 125 to provide an alert to thesubject or to a caregiver. The rehospitalization indication can includea risk factor for the subject, based on the trended physiologic signalcharacteristics, that the subject requires or will requirehospitalization.

Various Notes & Examples

Example 1 can include or use subject matter (such as an apparatus, asystem, a distributed system, a method, a means for performing acts, ora device readable medium including instructions that, when performed bythe device, can cause the device to perform acts), such as can includeor use multiple physiologic sensors configured to sense respectivephysiologic signals from a subject, and a heart failure analysis module.In Example 1, the heart failure analysis module is coupled to themultiple physiologic sensors. In Example 1, the heart failure analysismodule includes a processor circuit configured to identify ahospitalization event, and in response to the hospitalization event,perform one or more tasks. For example, in response to thehospitalization event, the processor circuit can be configured toidentify pre-hospitalization physiologic signal characteristicscorresponding to respective physiologic signals obtained using one ormore of the physiologic sensors, identify one or morepost-hospitalization physiologic signal characteristics that aredifferent than their corresponding one or more pre-hospitalizationphysiologic signal characteristics, the one or more post-hospitalizationphysiologic signal characteristics obtained using the same respectiveone or more physiologic sensors as the pre-hospitalization physiologicsignal characteristics, monitor a subsequent physiologic signal, afterthe hospitalization event, the subsequent physiologic signalcorresponding to one of the one or more post-hospitalization physiologicsignal characteristics that are different than their corresponding oneor more pre-hospitalization physiologic signal characteristics, thesubsequent physiologic signal obtained using the same one or morephysiologic sensors as the pre-hospitalization and post-hospitalizationphysiologic signal characteristics, and identify a subsequentphysiologic signal characteristic using the subsequent physiologicsignal. In an example, the processor circuit can be configured todetermine a heart failure parameter for the subject using informationabout the subsequent physiologic signal characteristic relative to itscorresponding pre-hospitalization physiologic signal characteristic.

Example 2 can include, or can optionally be combined with the subjectmatter of Example 1, to optionally include the processor circuitconfigured to update a therapy parameter for the subject using thedetermined heart failure parameter.

Example 3 can include, or can optionally be combined with the subjectmatter of one or any combination of Examples 1 or 2 to optionallyinclude the processor circuit configured to determine a parameterindicative of worsening heart failure when the subsequent physiologicsignal characteristic trends toward its correspondingpre-hospitalization physiologic signal characteristic.

Example 4 can include, or can optionally be combined with the subjectmatter of one or any combination of Examples 1 through 3 to optionallyinclude the processor circuit configured to identify the hospitalizationevent in response to a subject episode. In Example 4, the processorcircuit is optionally configured to identify pre-hospitalizationphysiologic signal characteristics including pre-episode physiologicsignal characteristics corresponding respectively to the physiologicsignals obtained using one or more of the physiologic sensors.

Example 5 can include, or can optionally be combined with the subjectmatter of one or any combination of Examples 1 through 4 to optionallyinclude the processor circuit configured to identify the hospitalizationevent in response to a subject heart failure decompensation episode.

Example 6 can include, or can optionally be combined with the subjectmatter of one or any combination of Examples 1 through 5 to optionallyinclude the processor circuit configured to provide a rehospitalizationindication when the subsequent physiologic signal characteristic trendstoward its corresponding pre-hospitalization physiologic signalcharacteristic.

Example 7 can include, or can optionally be combined with the subjectmatter of one or any combination of Examples 1 through 6 to optionallyinclude an implantable electrostimulation device coupled to the subject,wherein the processor circuit is configured to determine, based on thedetermined heart failure parameter, a therapy parameter for a therapyprovided by the implantable device to the subject, the therapy parameterincluding one of an AV delay, VV delay, an upper rate limit, a lowerrate limit, a magnitude of an electrostimulation pulse, a duration of anelectrostimulation pulse, a shape of an electrostimulation pulse, or alocation the electrostimulation pulse is delivered to the subject.

Example 8 can include, or can optionally be combined with the subjectmatter of one or any combination of Examples 1 through 7 to optionallyinclude, as one of the physiologic sensors, a heart sound sensorconfigured to provide a heart sound signal. In Example 8, the processorcircuit is optionally configured to monitor the heart sound signal,including to identify a pre-hospitalization heart sound amplitude usingthe heart sound signal and identify a post-hospitalization heart soundamplitude that is different than its corresponding pre-hospitalizationamplitude, the processor circuit is optionally configured to monitor, asthe subsequent physiologic signal, a subsequent heart sound amplitudeusing the heart sound sensor, and the processor circuit is optionallyconfigured to determine the heart failure parameter using informationabout whether the subsequent heart sound amplitude trends toward thepre-hospitalization heart sound amplitude.

Example 9 can include, or can optionally be combined with the subjectmatter of one or any combination of Examples 1 through 8 to optionallyinclude a heart sound sensor configured to provide a heart sound signal.In Example 9, the processor circuit is optionally configured to monitorthe heart sound signal, including to identify, as at least one of thepre-hospitalization physiologic signal characteristics, apre-hospitalization heart sound timing characteristic using the heartsound signal, the processor circuit is optionally configured toidentify, as at least one of the one or more post-hospitalizationphysiologic signal characteristics, a post-hospitalization heart soundtiming characteristic that is different than its correspondingpre-hospitalization timing characteristic, the processor circuit isoptionally configured to monitor, as the subsequent physiologic signal,a subsequent heart sound timing characteristic using the heart soundsensor, and the processor circuit is optionally configured to determinethe heart failure parameter using information about whether thesubsequent heart sound timing characteristic trends toward thepre-hospitalization heart sound timing characteristic.

Example 10 can include, or can optionally be combined with the subjectmatter of one or any combination of Examples 1 through 9 to optionallyinclude the processor circuit configured to provide a dischargerecommendation using the determined heart failure parameter.

Example 11 can include, or can optionally be combined with the subjectmatter of one or any combination of Examples 1 through 10 to optionallyinclude the processor circuit configured to identify, as the one or morepost-hospitalization physiologic signal characteristics that aredifferent than their corresponding one or more pre-hospitalizationphysiologic signal characteristics, one or more post-hospitalizationphysiologic signal characteristics indicative of an untreated portion ofsubject heart failure.

Example 12 can include, or can optionally be combined with the subjectmatter of one or any combination of Examples 1 through 11 to optionallyinclude the processor circuit configured to identify, as thepre-hospitalization physiologic signal characteristics, baselinephysiologic signal characteristics corresponding to the multiplephysiologic signals obtained using the one or more physiologic sensors.

Example 13 can include, or can optionally be combined with the subjectmatter of Example 12, to optionally include the processor circuitconfigured to determine the heart failure parameter by automaticallyprocessing information about the subsequent physiologic signalcharacteristic relative to its corresponding baseline physiologic signalcharacteristic.

Example 14 can include, or can optionally be combined with the subjectmatter of Example 13, to optionally include the processor circuitconfigured to provide an indication of worsening heart failure when thesubsequent physiologic signal characteristic is substantially unchangedor trends away from its corresponding baseline physiologic signalcharacteristic.

Example 15 can include, or can optionally be combined with the subjectmatter of Example 14, to optionally include the processor circuitconfigured to generate a rehospitalization alert using the indication ofworsening heart failure.

Example 16 can include, or can optionally be combined with the subjectmatter of one or any combination of Examples 1 through 15 to optionallyinclude the processor circuit configured to automatically processinformation about the subsequent physiologic signal characteristicrelative to its corresponding pre-hospitalization physiologic signalcharacteristic during a specified post-hospitalization interval.

Example 17 can include, or can optionally be combined with the subjectmatter of one or any combination of Examples 1 through 16 to optionallyinclude the processor circuit configured to identify, as one or more ofthe pre-hospitalization physiologic signal characteristics, thepost-hospitalization physiologic signal characteristics, and thesubsequent physiologic signal characteristic, respective morphologicsignal features, of the same type, of the multiple physiologic signals.

Example 18 can include, or can optionally be combined with the subjectmatter of one or any combination of Examples 1 through 17 to optionallyinclude an implantable medical device and a memory circuit, coupled tothe implantable medical device, wherein the multiple physiologic sensorsare coupled to the memory circuit, and the memory circuit is configuredto store information about the respective physiologic signals from thesubject sensed using the multiple physiologic sensors, and wherein theprocessor circuit is configured to determine the heart failure parameterusing the information stored in the memory circuit, including usinginformation about a pre-hospitalization physiologic signalcharacteristic.

Example 19 can include, or can optionally be combined with the subjectmatter of one or any combination of Examples 1 through 18 to include,subject matter (such as an apparatus, a system, a distributed system, amethod, a means for performing acts, or a machine readable mediumincluding instructions that, when performed by the machine, that cancause the machine to perform acts), such as can include monitoringmultiple physiologic signals obtained using corresponding physiologicsensors, identifying subject-specific baseline characteristicscorresponding respectively to the physiologic signals obtained using thephysiologic sensors, and identifying a hospitalization event. Example 19can optionally include, in response to the hospitalization event, one ormore of identifying one or more post-hospitalization physiologic signalcharacteristics that are different than their corresponding baselinecharacteristics, the one or more post-hospitalization physiologic signalcharacteristics obtained using the same respective one or morephysiologic sensors as the baseline characteristics, monitoring asubsequent physiologic signal, after the hospitalization event, thesubsequent physiologic signal corresponding to one of the one or morepost-hospitalization physiologic signal characteristics, using the sameone or more physiologic sensors for the baseline characteristics and thepost-hospitalization physiologic signal characteristics, identifying asubsequent physiologic signal characteristic using the subsequentphysiologic signal, and determining a heart failure parameter for thesubject using a processor circuit to automatically process informationabout the subsequent physiologic signal characteristic relative to itscorresponding post-hospitalization physiologic signal characteristic andits corresponding baseline characteristic.

Example 20 can include, or can optionally be combined with the subjectmatter of Example 19, to optionally include updating a device therapyparameter when the subsequent physiologic signal characteristic issubstantially unchanged from its corresponding post-hospitalizationphysiologic signal after a predetermined interval.

Example 21 can include, or can optionally be combined with the subjectmatter of one or any combination of Examples 1 through 20 to include,subject matter (such as an apparatus, a system, a distributed system, amethod, a means for performing acts, or a machine readable mediumincluding instructions that, when performed by the machine, that cancause the machine to perform acts), such as can include multiplephysiologic sensors coupled to an implantable medical device andconfigured to sense respective physiologic signals, and a heart failureanalysis module, coupled to the multiple physiologic sensors. In Example21, the heart failure analysis module optionally includes one or moreprocessor circuits configured to, individually or collectively, receivepre-episode physiologic signal characteristics corresponding to themultiple physiologic signals obtained using one or more of thephysiologic sensors, receive one or more post-treatment physiologicsignal characteristics that are of the same type and different thantheir corresponding one or more pre-episode physiologic signalcharacteristics, the one or more post-treatment physiologic signalcharacteristics obtained using the same one or more physiologic sensorsas the pre-episode physiologic signal characteristics, receive asubsequent physiologic signal, after a hospitalization period thatincludes a subject treatment, the subsequent physiologic signalcorresponding to one of the one or more post-treatment physiologicsignal characteristics, the subsequent physiologic signal obtained usingthe same one or more physiologic sensors as the pre-episode physiologicsignal characteristics and the post-treatment physiologic signalcharacteristics, identify a subsequent physiologic signal characteristicusing the subsequent physiologic signal, and update a therapy providedby the implantable medical device using information about the subsequentphysiologic signal characteristic relative to its correspondingpre-episode physiologic signal characteristic.

Example 22 can include, or can optionally be combined with the subjectmatter of one or any combination of Examples 1 through 21 to include,subject matter (such as an apparatus, a system, a distributed system, amethod, a means for performing acts, or a machine readable mediumincluding instructions that, when performed by the machine, that cancause the machine to perform acts), such as can include a processorcircuit comprising a data input configured to receive physiologicinformation about a subject using multiple corresponding physiologicsensors, and a data output configured to provide a heart failureparameter for the subject. In Example 22, the processor is optionallyconfigured to monitor multiple physiologic signals obtained using thedata input and corresponding physiologic sensors, receive an indicationof a hospitalization event, and in response to the hospitalizationevent, identify pre-hospitalization physiologic signal characteristicscorresponding to respective physiologic signals obtained using one ormore of the physiologic sensors, identify one or morepost-hospitalization physiologic signal characteristics that aredifferent than their corresponding one or more pre-hospitalizationphysiologic signal characteristics, the one or more post-hospitalizationphysiologic signal characteristics obtained using the same respectiveone or more physiologic sensors as the pre-hospitalization physiologicsignal characteristics, monitor a subsequent physiologic signal, afterthe hospitalization event, the subsequent physiologic signalcorresponding to one of the one or more post-hospitalization physiologicsignal characteristics that are different than their corresponding oneor more pre-hospitalization physiologic signal characteristics, thesubsequent physiologic signal obtained using the same one or morephysiologic sensors as the pre-hospitalization and post-hospitalizationphysiologic signal characteristics, identify a subsequent physiologicsignal characteristic using the subsequent physiologic signal, anddetermine a relationship of the subsequent physiologic signalcharacteristic relative to its corresponding pre-hospitalizationphysiologic signal characteristic to provide the heart failure parameterfor the subject.

Each of these non-limiting examples can stand on its own, or can becombined in various permutations or combinations with one or more of theother examples.

The above detailed description includes references to the accompanyingdrawings, which form a part of the detailed description. The drawingsshow, by way of illustration, specific embodiments in which theinvention can be practiced. These embodiments are also referred toherein as “examples.” Such examples can include elements in addition tothose shown or described. However, the present inventors alsocontemplate examples in which only those elements shown or described areprovided. Moreover, the present inventors also contemplate examplesusing any combination or permutation of those elements shown ordescribed (or one or more aspects thereof), either with respect to aparticular example (or one or more aspects thereof), or with respect toother examples (or one or more aspects thereof) shown or describedherein.

In the event of inconsistent usages between this document and anydocuments so incorporated by reference, the usage in this documentcontrols.

In this document, the terms “a” or “an” are used, as is common in patentdocuments, to include one or more than one, independent of any otherinstances or usages of “at least one” or “one or more.” In thisdocument, the term “or” is used to refer to a nonexclusive or, such that“A or B” includes “A but not B,” “B but not A,” and “A and B,” unlessotherwise indicated. In this document, the terms “including” and “inwhich” are used as the plain-English equivalents of the respective terms“comprising” and “wherein.” Also, in the following claims, the terms“including” and “comprising” are open-ended, that is, a system, device,article, composition, formulation, or process that includes elements inaddition to those listed after such a term in a claim are still deemedto fall within the scope of that claim. Moreover, in the followingclaims, the terms “first,” “second,” and “third,” etc. are used merelyas labels, and are not intended to impose numerical requirements ontheir objects.

Method examples described herein can be machine or computer-implementedat least in part. Some examples can include a computer-readable mediumor machine-readable medium encoded with instructions operable toconfigure an electronic device to perform methods as described in theabove examples. An implementation of such methods can include code, suchas microcode, assembly language code, a higher-level language code, orthe like. Such code can include computer readable instructions forperforming various methods. The code may form portions of computerprogram products. Further, in an example, the code can be tangiblystored on one or more volatile, non-transitory, or non-volatile tangiblecomputer-readable media, such as during execution or at other times.Examples of these tangible computer-readable media can include, but arenot limited to, hard disks, removable magnetic disks, removable opticaldisks (e.g., compact disks and digital video disks), magnetic cassettes,memory cards or sticks, random access memories (RAMs), read onlymemories (ROMs), and the like.

The above description is intended to be illustrative, and notrestrictive. For example, the above-described examples (or one or moreaspects thereof) may be used in combination with each other. Otherembodiments can be used, such as by one of ordinary skill in the artupon reviewing the above description. The Abstract is provided to complywith 37 C.F.R. § 1.72(b), to allow the reader to quickly ascertain thenature of the technical disclosure. It is submitted with theunderstanding that it will not be used to interpret or limit the scopeor meaning of the claims. Also, in the above Detailed Description,various features may be grouped together to streamline the disclosure.This should not be interpreted as intending that an unclaimed disclosedfeature is essential to any claim. Rather, inventive subject matter maylie in less than all features of a particular disclosed embodiment.Thus, the following claims are hereby incorporated into the DetailedDescription as examples or embodiments, with each claim standing on itsown as a separate embodiment, and it is contemplated that suchembodiments can be combined with each other in various combinations orpermutations. The scope of the invention should be determined withreference to the appended claims, along with the full scope ofequivalents to which such claims are entitled.

1. (canceled)
 2. A system comprising: a physiologic sensor configured tosense a physiologic signal from a subject; and a heart failure analysismodule, coupled to the physiologic sensor, the heart failure analysismodule including a processor circuit configured to: at discharge from ahospitalization event, identify a first physiologic signalcharacteristic corresponding to the physiologic signal; after aspecified duration following the discharge from the hospitalizationevent, identify a second physiologic signal characteristic correspondingto the physiologic signal; determine whether the second physiologicsignal characteristic is substantially unchanged from the firstphysiologic signal characteristic; and provide a rehospitalizationindication when the second physiologic signal characteristic isdetermined to be substantially unchanged from the first physiologicsignal characteristic.
 3. The system of claim 2, wherein the processorcircuit is configured to provide the rehospitalization indication whenthe second physiologic signal characteristic does not approach a knownbaseline signal characteristic for the physiologic signal.
 4. The systemof claim 2, wherein the processor circuit is configured to: determinewhether the second physiologic signal characteristic is substantiallyunchanged from an earlier physiologic signal characteristic identifiedprior to the discharge from the hospitalization event; and provide therehospitalization indication when the second physiologic signalcharacteristic is substantially unchanged from the earlier physiologicsignal characteristic.
 5. The system of claim 2, further comprising anelectrical energy delivery circuit configured to generate aelectrostimulation therapy for the subject, wherein the processorcircuit is configured to adjust the electrostimulation therapy based onthe second physiologic signal characteristic being substantiallyunchanged from the first physiologic signal characteristic.
 6. Thesystem of claim 2, wherein the processor circuit is configured toprovide the rehospitalization indication when the second physiologicsignal characteristic is different from a known baseline signalcharacteristic for the physiologic signal.
 7. The system of claim 2,wherein the physiologic sensor includes a heart sound sensor, andwherein the physiologic signal includes a heart sound signal sensedusing the heart sound sensor.
 8. The system of claim 2, wherein thephysiologic sensor includes a respiration sensor, and wherein thephysiologic signal includes a respiration signal sensed using therespiration sensor.
 9. The system of claim 2, wherein the physiologicsensor includes a tidal volume sensor, and wherein the physiologicsignal includes a tidal volume signal sensed using the tidal volumesensor.
 10. The system of claim 2, further comprising at least a secondphysiologic sensor configured to sense a different physiologic signalfrom the subject; wherein the heart failure analysis module is coupledto the second physiologic sensor; and wherein the processor circuit isconfigured to withhold the rehospitalization indication when thedifferent physiologic signal substantially corresponds with a knownbaseline signal level.
 11. The system of claim 2, comprising animplantable electrostimulation device coupled to the subject, whereinthe processor circuit is configured to use the physiologic signal todetermine a heart failure parameter and a therapy parameter for atherapy provided to the subject by the implantable device based on theheart failure parameter, the therapy parameter including one of an AVdelay, VV delay, an upper rate limit, a lower rate limit, a magnitude ofan electrostimulation pulse, a duration of an electrostimulation pulse,a shape of an electrostimulation pulse, or a location for theelectrostimulation pulse to be delivered to the subject.
 12. The systemof claim 2, further comprising an implantable medical device; and amemory circuit, coupled to the implantable medical device; wherein thephysiologic sensor is coupled to the memory circuit, and the memorycircuit is configured to store information about the physiologic signalfrom the subject sensed using the physiologic sensor; and wherein theprocessor circuit is configured to provide the rehospitalizationindication using the information stored in the memory circuit, includingusing information about a pre-hospitalization physiologic signalcharacteristic identified prior to the discharge from thehospitalization event.
 13. The system of claim 2, wherein the processorcircuit is configured to identify the first physiologic signalcharacteristic responsive to receiving an indication of the dischargefrom the hospitalization event.
 14. A system comprising: a physiologicsensor configured to sense a physiologic signal from a subject; and aheart failure analysis module, coupled to the physiologic sensor, theheart failure analysis module including a processor circuit configuredto: at discharge from a hospitalization event, identify a firstphysiologic signal characteristic corresponding to the physiologicsignal; after a specified duration following the discharge from thehospitalization event, identify a subsequent physiologic signalcharacteristic corresponding to the physiologic signal; and provide arehospitalization recommendation when a difference between a knownbaseline characteristic and the first physiologic signal characteristicis substantially the same as a difference between the known baselinecharacteristic and the subsequent physiologic signal characteristic. 15.The system of claim 14, wherein the physiologic sensor includes a heartsound sensor, and wherein the physiologic signal includes a heart soundsignal sensed using the heart sound sensor.
 16. The system of claim 14,wherein the physiologic sensor includes a respiration sensor, andwherein the physiologic signal includes a respiration signal sensedusing the respiration sensor.
 17. A method comprising: monitoring aphysiologic signal received from a physiologic sensor; identifying asubject-specific first physiologic signal characteristic correspondingto the physiologic signal and at discharge from a hospitalization event;identifying a second physiologic signal characteristic corresponding tothe physiologic signal and after a specified duration following thedischarge from the hospitalization event; determining whether the secondphysiologic signal characteristic is substantially unchanged from thefirst physiologic signal characteristic; and providing arehospitalization indication when the second physiologic signalcharacteristic is determined to be substantially unchanged from thefirst physiologic signal characteristic.
 18. The method of claim 17,further comprising monitoring at least one other physiologic signal overan interval between an onset of the hospitalization event and thedischarge from the hospitalization event, wherein a characteristic ofthe other physiologic signal trends toward a corresponding baselinecharacteristic value during the interval.
 19. The method of claim 17,further comprising determining a difference between the secondphysiologic signal characteristic and a corresponding baselinecharacteristic value for the physiologic signal; wherein providing therehospitalization indication includes using information about thedifference.
 20. The method of claim 17, further comprising generating asubject therapy, using an implantable medical device, in response to therehospitalization indication.
 21. The method of claim 17, furthercomprising identifying a second physiologic signal having acharacteristic that changed in response to a therapy administeredfollowing the hospitalization event; identifying information about atrend of the characteristic of the second physiologic signal followingthe discharge from the hospitalization event; and providing therehospitalization indication based in part on the information about thetrend of the characteristic of the second physiologic signal followingthe discharge from the hospitalization event.